(a) Field of the Invention
This invention relates to 3-(4- or 3-pyridinyl)-2-cyclohexen-1-ones, to processes for their preparation and to a process for converting them to 3-(4- or 3-pyridinyl)anilines, which are useful as intermediates for preparing known antibacterial agents.
(B) Description of the Prior Art
The term "pyridyl" used in the following presentation of the prior art has the same meaning as "pyridinyl", the preferred term now used in Chemical Abstracts and used hereinbelow in describing the instant invention.
H. Beyer et al. [Chem. Ber. 90, 592-8 (1957)] show the reaction of 2-pyridylacetone with methyl vinyl ketone to produce 3-methyl-6-(2-pyridyl)-2-cyclohexen-1-one and its conversion by heating with sulfur to produce 3-methyl-6-(2-pyridyl)phenol.
C. S. Marvel et al. [J. Org. Chem. 22, 1451-1457 (1957)] report the following side reaction:
"The synthesis (of ethyl pyridalacetoacetates) was first attempted with pyridine-3-aldehyde by the method of Knoevenagel [Ber., 29, 172 (1896)], but it became apparent that even at the low temperature (-20.degree. ) or during subsequent steps a large amount of Michael addition of acetoacetic ester to ethyl 2-(3'-pyridal)acetoacetate (VII) was taking place, since distillation after the decarboxylation step yielded a 3-methyl-5-(3'-pyridyl)-.DELTA..sup.2 -cyclohexenone (I). (The position of the double bond had not been definitely fixed in the cyclohexenone ring. ##STR1## It may have migrated to the .DELTA..sup.5 position.) In order to avoid this side reaction, the condensation was run in an ether solution. In this manner the product crystallized as it was formed, and the ethyl 2-pyridalacetoacetates were obtained relatively free from acetoacetic ester." PA1 "In the acetoethylation of 2-phenacylpyridine (XXIII) two compounds, XXIV and XXV, were obtained. In this connection, it should be pointed out that earlier 2-phenacylpyridine hydrochloride had been treated with methyl vinyl ketone and alcoholic potassium hydroxide by Beyer et al. ##STR2## [H. Beyer, W. Lassig, and G. Schudy, Ber., 90, 592 (1957)], who obtained a compound, m.p. 166.degree.. Although they did not elucidate its structure, these workers claim that they obtained XXIV. From our work there is little doubt that they prepared XXV."
N. C. Ross et al. [J. Org. Chem. 29, 2341-2350 (1964)] show the steps of reacting acetophenone with methyl vinyl ketone in the presence of lithium amide in anhydrous liquid ammonia to produce 1-phenylhexan-1,5-dione together with a cyclized product, 3-phenyl-3-hydroxycyclohexanone, which by dehydration is converted into 3-phenyl-2-cyclohexen-1-one. Ross et al. also report the following reaction
P. L. Compagnon et al. [Bull. Soc. Chim. Fr. 10, 4132-6 (1968] show the hydration of 7-(2-pyridyl)-1,2-heptyn-6-one in the presence of mecuric salts to produce a transitory 7-(2-pyridyl)heptan-2,6-dione which is said to automatically lose a molecule of water to produce 2-(2-pyridyl)-3-methyl-2-cyclohexen-1-one which is then catalytically hydrogenated in the presence of Raney nickel to produce 2-(2-pyridyl)-3-methylcyclohexan-1-one.
H. Mohrle et al. [Arch. Pharmazie 307, 550-560 (1974)] show the reaction of pyridine-3-aldehyde with two moles of ethyl acetoacetate and conversion of the resulting condensation product at -10.degree. C. in the presence of diethylamine to produce 3-methyl-5-(3-pyridyl)-2-cyclohexen-1-one. Also, they established by use of NMR spectrum of said 2-cyclohexen-1-one that its double bond is at the 2-3 position instead of the 5-6 position, which had been presented by Marvel et al., supra, as a possibility.
F. M. Beringer et al. [J. Am. Chem. Soc. 75, 2635-2639 (1953)] show the preparation of 3-methyl-5-phenyl-2-cyclohexen-1-one from ethyl .alpha.,.alpha.-diacetyl-.beta.-phenylglutarate, reaction of the 3-methyl-5-phenyl-2-cyclohexen-1-one with hydroxylamine hydrochloride to produce its oxime and then heating the oxime successively with acetic anhydride and then acetyl chloride to produce 3-methyl-5-phenylacetanilide and hydrolysis of said acetanilide with aqueous hydrochloric acid to produce 3-methyl-5-phenylaniline.